The present invention relates to a method for determining at least one parameter of samples of physiological liquids, to test devices which may be used in the method, to a holder comprising a plurality of such test devices, and to a measuring apparatus adapted to accommodate the holder and to be used in the method and to a system comprising the apparatus and the holder.
In particular, the present invention relates to methods and systems in which an operator, after sample taking, is protected from contact with physiological liquids, such as blood, plasma, urine, etc.
In human medicine, it has hitherto been customary practice to send samples of physiological liquids, e.g. blood, plasma or urine, for analysis to a specialized clinical laboratory possessing the necessary technical equipment and trained staff.
In the past, clinical chemical analysis systems have tended to be large in size, expensive and complex to operate, and in general only relatively large medical institutions have been able to afford the purchase, operation and maintenance of such systems. Smaller hospitals, clinics, general practitioners etc. usually have had to employ centralized commercial or hospital laboratories for clinical chemical analyses, leading to unavoidable delays in the procedure.
Since abnormal values of certain clinical chemical parameters are indicative of serious danger to health, the rapid and reliable determination of clinical chemical parameters in general is of crucial importance for proper and effective medical treatment. Furthermore, quite apart from the acute aspects of medical treatment, it is clearly an advantage, both for patients from a psychological viewpoint and for medical staff from an administrative viewpoint, that clinical analysis results are accessible as quickly as possible.
Thus, increasing demands for reduction in costs, more rapid turnover, greater decentralisation and increased staff flexibility in clinical chemical analysis have provided an incentive for the development of easy-to-use, easy-to-maintain, reliable, relatively cheap, compact and, if possible, portable equipment, based in part on discardable components, for the bedside measurement of those characteristics of chemical species which constitute fundamental clinical chemical parameters of physiological liquids.
In WO 89/04474, a portable apparatus for measuring the electrochemical characteristics of a sample is disclosed, which apparatus includes a shell which houses a cartridge bay adapted to receive, from a U-shaped clip, a plurality of disposable cartridges for receiving samples. A desired number of cartridges are manually loaded onto the clip and the clip is manually loaded into the cartridge bay whereby the cartridges are loaded into the apparatus. After loading, the clip is removed and discarded. A blood sample may now be dispensed into a specific cartridge in a measurement position in the apparatus from a sample containing syringe. After a measurement, the used cartridge is ejected from the apparatus.
It is a disadvantage of the above-mentioned apparatus that an operator and the environment of the apparatus is exposed to contact with the sample in a used cartridge after ejection of the cartridge from the apparatus.
The AVL Scientific Corporation has introduced the AVL OPTI 1 portable blood gas analyzer in which a disposable cassette adapted to receive a blood sample is inserted into the analyzer during a measurement. The blood sample may be supplied from a syringe or a capillary, which may be attached to the cassette and discarded with the cassette after a measurement. The disengagement and subsequent handling of this contaminated cassette is performed manually and, thus, subjects the operator to a risk of getting into contact with the sample.
It is an object of the present invention to provide a method and an apparatus for analysis of physiological liquids that provide maximum protection of laboratory staff from contact with a physiological liquid after sample taking.
It is another object of the present invention to provide a method and apparatus for analysis of physiological liquids in which a plurality of test devices can be inserted into the measuring apparatus in one operation and can be removed from the measuring apparatus in one operation whereby the number of manual operations needed to perform a determination of parameters of physiological liquids are minimized.
It is yet another object of the invention to provide a test device for use in a holder for holding the test device that both protect the environment from spills of samples and both provide maximum protection of laboratory staff from contact with physiological liquid after sample taking.
It is a further object of the invention to provide a test device adapted to receive and hold at least a part of a sampling device supplying the sample to the test device, so that the at least part of the sampling device can be discarded with the test device.
In a first aspect, the present invention relates to a method for determining at least one parameter of samples of physiological liquids, the method comprising
arranging a plurality of test devices in a holder,
loading, to at least one of the test devices, a sample of a physiological liquid,
determining the at least one parameter of the sample loaded to the at least one test device, the at least one test device being retained in the holder after the determination,
and discarding the holder with the at least one test device retained therein in such a manner that the at least one test device is substantially separated from the ambience, thus reducing the risk of contact between an operator and sample loaded to the at least one test device.
Parameters of physiological liquids of particular interest are, for example:
pH,
concentrations of electrolytes, such as Li+, Na+, K+, Ca2+, Mg2+, Clxe2x88x92, HCO3xe2x88x92and NH3 (NH4+),
concentrations of dissolved gases, notably oxygen and carbon dioxide (conventionally reported in the form of partial pressures, e.g. pO2, pCO2),
haemoglobin concentration, concentration of haemoglobin derivatives,
concentrations of metabolic factors, such as glucose, creatinine, urea (BUN), uric acid, lactic acid, pyruvic acid, ascorbic acid, phosphate, protein, bilirubin, cholesterol, triglycerides, phenylalanine and tyrosine,
concentrations of enzymes, such as lactic acid dehydrogenase (LDH), lipase, amylase, choline esterase, alkaline phosphatase, acid phosphatase, alanine amino transferase (ALAT), aspartate amino transferase (ASAT) and creatinine kinase (CK),
and concentrations of ligands, such as antibodies and nucleotide fragments.
According to the present invention a parameter of a physiological liquid may be determined by any known suitable method, such as optical methods, such as measurement of absorption, scattering, diffraction, reflection, refraction, luminescence, fluorescence, phosphorescence, etc., in specific wavelength ranges of the electromagnetic spectrum, sensor response measurement methods, etc.
The term xe2x80x9csensorxe2x80x9d as used here denotes any kind of organ of which some part, in the present context called the sensing part, is capable
either of
selective interaction with the chemical species of interest, thereby producing a well-defined and measurable response which is a function of the desired characteristic of that chemical species, the desired characteristic thus being derivable therefrom,
or of
response to a bulk property of a liquid, the response not being selective with respect to any specific chemical species, but being a function of the total concentration of one or more chemical species in the liquid, the desired characteristic thus being derivable therefrom.
Relevant types of sensors are those adapted to determine any of the previously mentioned clinical chemical parameters, for example:
potentiometric sensors for use in aqueous media, such as ion-selective electrodes for specific measurement of the concentration of selected ionic chemical species [a description of non-limiting examples of some ion-selective electrodes for the selective measurement of the concentrations of a number of cations and anions of frequent interest is provided by Simon (W. Simon, xe2x80x9cIon-Selective Electrodes Based on Neutral Carriersxe2x80x9d, in H. Freiser, Ed., xe2x80x9cIon-Selective Electrodes in Analytical Chemistryxe2x80x9d, Plenum, 1978, pp. 211-281)], the response being in the form of an electric potential,
amperometric sensors, such as sensors for the determination of oxygen partial pressure, whose response is in the form of an electric current,
optical sensors, such as sensors producing a colour response to a particular chemical species, the colour intensity being measured by, e.g., reflectometry,
piezoelectric sensors,
thermometric sensors,
pressure-change sensors,
acoustic sensors,
enzyme-based sensors employing an enzymatic reaction and generating a response on the basis of any relevant physical principle, for example any of those principles employed in the sensor types listed above; examples are enzyme-based thermistors and enzyme-based amperometric sensors for use in the measurement of concentrations of metabolic products, e.g. glucose, urea, creatinine or lactate,
and affinity sensors comprising one moiety of an affinity pair, e.g. an antigen/antibody pair or two complementary nucleotide fragments, the other moiety being the chemical species of interest.
Sensors generally perform a conversion function to convert the energy form associated with the change occurring at the sensing surface part to electrical energy or electromagnetic radiant energy, the sensor response thereby being registerable in the form of an electrical or optical signal. A more detailed description of non-limiting examples of conversion principles which are relevant in connection with sensors is given by Middelhoek and Noorlag (S. Middelhoek and D. J. W. Noorlag, xe2x80x9cThree-Dimensional Representation of Input and Output Transducersxe2x80x9d, Sensors and Actuators 2, 1981/1982, pp. 29-41). The test device may have any appropriate configuration as described in the numerous patents, such as U.S. Pat. Nos. 4,053,381, 4,269,803, GB 2 090 659, WO 90/02938, U.S. Pat. No. 4,301,412, WO 89/04474, etc., and publications related to test devices or as commercially available. The sample may be loaded to a surface or a cavity of the test device.
It should be noted that the sample of the physiological liquid may be a pre-treated sample of the physiological sample. This pre-treatment may vary depending on the actual determination or determinations to be performed or the parameter or parameters to be determined. If a determination requires the addition of a reagent to the sample, this reagent may be added before the sample being loaded to the test device or it may be provided with the test device from the manufacturer.
In the event that the reagent will deteriorate other determinations, it may be preferred to add this reagent to e.g. a measuring chamber in the test device only used for the actual determination or only determinations not deteriorated by the agent.
Another factor to be taken into account is the timing of the addition of the reagent. It may be preferred to add the reagent as early as possible to either allow it to react with the sample in as large a period of time as possible or in order to e.g. prevent deterioration or alteration of the sample prior to determination.
An early addition of reagent may for example be obtained by having the reagent preloaded onto a sampling device used for the transfer of the sample from the patient to the test device. The reagent may be selected among compounds interacting with the chemical parameter or species under test and compounds needed for other purposes such as anticoagulants e.g. heparin, citrate or EDTA. Such anticoagulants are typically added to blood samples immediately after withdrawal of the blood from the patient.
According to this first aspect of the invention, the test device holding the sample is retained in a holder wherein the operator cannot gain access to the sample. When discarding the test device or test devices, the holder containing test devices is discarded. In this manner, the operator is not subjected to any hazards by these operations.
In the present context, the term that a test device is xe2x80x9csubstantially separated from the ambiencexe2x80x9d means that the test devices cannot accidentally leave the holder and that an operator cannot access the devices without using a tool.
It is an important advantage of the present invention that no parts of the test device can be accessed by an operator at the time where the operator has to remove or replace the device.
It is another advantage of the method according to the invention that the holder holds a plurality of test devices. Thereby, the operator need neither insert a new test device in the system nor remove a used test device from the system each time a determination of parameters has to be performed. Instead, a batch of test devices is inserted into the system in one operation and is removed from the system in one operation.
It is preferred that a plurality of samples of physiological liquids are introduced into respective test devices of the plurality of test devices, the at least one parameter of each sample is determined, the plurality of test devices loaded with samples the at least one parameter of which has been determined being retained in the holder, and that the holder is discarded with the test devices retained therein.
Thus, subsequent to determination of a parameter of a physiological liquid, the test devices are enclosed in the holder and inaccessible to the operator.
In order to further protect the operator from contact with physiological liquids, a sampling device for obtaining the sample from a patient or a part of the device may be received by the holder and discarded with the holder. For example, each test device may be adapted to receive and hold the sampling device or a part of thereof so that the (part of the) sampling device may be retained in the holder with the corresponding test device and may be discarded with the holder.
Even though access to any test devices in the holder which has not yet received a sample may not be hazardous to the operator (this depends on e.g. reagents present on or in the test devices for use in the determinations), it is preferred that a test device is transferred to an operational position prior to being loaded with a sample and that test devices not occupying an operational position are retained in the holder in such a manner that they are substantially separated from the ambience.
The test device may be adapted to receive and hold the sample in a liquid tight enclosure so that the sample is loaded to the device by introducing the sample into the device, e.g. by aspiration, and so that the environment and an operator is protected from contact with the sample.
A disinfectant may be provided in the test device. Most preferably the disinfectant is added to the test device during the manufacturing process. In the ready-to-use device the disinfectant may be present as a dry substance or in wet form and may be located in any suitable location in the test device. The presence of a disinfectant in the test device will prevent microbiological growth in the sample and among other things obviate or greatly reduce any smell inconveniences from spent test devices.
Further, a chemical substance detectable by the measuring apparatus per se or upon conversion may be provided to the test device as a label. When appropriately designed the measuring apparatus may be able to distinguish between labelled and unlabelled test devices.
This feature may be utilized to prevent use of non-authentic test devices.
In a second aspect, the invention relates to a system for determining at least one parameter of at least one sample of a physiological liquid, the system comprising
a holder adapted to receive a plurality of test devices,
a measuring apparatus comprising
means for receiving and operationally engaging with the holder,
a measuring station comprising means for determining said at least one parameter of a sample loaded to a test device, and
means for moving one or more test devices in the holder in relation to the measuring station so as to position individual devices held in the holder in operational communication with the measuring station,
the holder being adapted to substantially separate, from the ambience, any test device held therein loaded with a sample, thus allowing the holder with the sample-holding test device or devices to be discarded without any substantial risk of contact between an operator and the sample.
The term xe2x80x9coperational communicationxe2x80x9d means that the measuring station and the one or more test devices is or are positioned in relation to each other in such a way that determinations of parameters of the sample(s) in the one or more test devices can be performed. The one or more test devices may be moved in relation to a fixed measurement station or the measurement station may be moved in relation to fixed test device(s).
Preferably, the present system comprises test device moving means for moving a test device which is to be moved into operational communication with the measuring station between a starting position in the holder, a sample loading position, and one or more measurement positions in which the test device is operationally positioned for measurement.
The holder may comprise a holder memory means for storage of data and the measuring apparatus may comprise means for reading the data contained in the holder memory means.
The data may comprise an expiry date of the test devices comprised by the holder, identification data, calibration data, etc.
Preferably, the means for reading data contained in the holder memory means comprise expiration date detection means for detection of the expiration date of the holder.
The system may prompt the operator, if a holder that is brought into engagement with the measuring apparatus of the system holds test devices which are no longer usable.
Further, the system may comprise first rejection means for preventing measurements with a holder containing test devices which have expired, to prevent that measurements using defective test devices are performed.
The means for reading data contained in the holder memory means may comprise detection means for detecting identification data of the holder.
The system may prompt the operator, if a holder with invalid identification data or no identification data is brought into engagement with the measuring apparatus.
The system may also comprise second rejection means for preventing measurements with a holder with invalid identification data or no identification data.
Different holders may hold test devices of different kinds, each kind of test device being adapted for determination of specific parameters. Each kind of test device may require the measuring system to execute specific operations during a determination. The holder memory means may contain data for specifying the specific operations to be executed by the measuring apparatus when in operational engagement with the corresponding holder.
In a third aspect, the present invention relates to a holder adapted to hold a plurality of test devices and having
means for exposing at least one test device to measurement of at least one parameter of a sample loaded to the device, and means for substantially separating, from the ambience, any test device held therein loaded with a sample, thus allowing the holder with the sample-holding device or devices to be handled without any substantial risk of contact between an operator and the sample.
In the present context, xe2x80x9cmeans for exposing at least one test device to measurementxe2x80x9d may e.g. be one or more openings in the holder through which a measuring apparatus may gain access to the at least one test device, or it may be means for moving the at least one test device to a position in relation to a measuring apparatus or for moving a measuring apparatus to a position in relation to the at least one test device.
The holder preferably comprises a number of compartments each of which is adapted to hold one test device. Alternatively, the holder may comprise two compartments: for holding the unused and the used test devices, respectively.
Preferably, each compartment can change between a closed state, in which the test device(s) contained therein is/are substantially separated from the ambience, and an open state, in which the test device(s) contained therein is/are available to the ambience.
In order to reduce the risk of exposure of an operator to used test devices, preferably only one or a few of the compartments at a time can be in the open state.
The holder preferably holds a number of test devices being equal to or smaller than the number of compartments which are in a closed state, so that all contaminated test devices may be enclosed in the holder.
Preferably, the holder will comprise a holder housing and a holder member positioned in the holder housing.
A compartment in a closed state is preferably defined partly by structural elements of the member and partly by a wall part of the housing.
A compartment in an open state is preferably defined by structural elements of the member, the wall part of the housing co-operating with that compartment defining an opening therein allowing access of a test device contained therein to the ambience.
Even though virtually any shape and form of the holder may be contemplated, the presently preferred holder has a holder member being a substantially cylindrical drum positioned rotatably about a centre axis of the drum in the holder housing.
According to a preferred embodiment of the invention, the drum further comprises an inner cylindrical surface and a number of wall parts extending outwardly from the inner cylindrical surface, structural elements of the member partly defining the compartments comprising the outwardly extending wall parts.
The holder may comprise indicator means indicating the state of use of the test devices held in the holder. This is in particular advantageous when only a part of the test devices in the holder have been used when the holder is disengaged from the measuring apparatus. When the holder is re-engaged in the measuring apparatus, utilisation of the indicator means ensures that test devices containing samples are not brought into operational communication with the measuring apparatus.
The holder may comprise holder memory means for storage of data, such as an expiration date, calibration data of the test devices held in the holder, identification data, etc.
The holder memory means may comprise a bar code label or may comprise a more sophisticated electronic memory, such as a ROM, RAM, PROM, EPROM, E2PROM, a magnetic strip, or an optically readable memory.
In order to further ensure that an operator cannot gain access to physiological liquid in the holder, such as sample spilled inside the holder, the holder preferably also comprises means for retaining sample wasted in the holder. These means may be positioned close to any openings of the holder, in order to prevent any spilled liquid sample to gain access to the outside of the holder.
A disinfectant may be provided in the holder. Most preferably the disinfectant is added to the holder during the manufacturing process. In the ready-to-use holder the disinfectant may be present as a dry substance or in wet form and may be located in any suitable location in the holder. The presence of a disinfectant in the holder will prevent microbiological growth in any sample waste and among other things obviate or greatly reduce any smell inconveniences from the holder.
In a fourth aspect, the present invention relates to a test device for receiving a sample of a physiological liquid and comprising
a substantially sealed housing having a sample inlet port defined therein for entrance of the sample into the housing, the housing comprising at least one measuring chamber adapted for measurement of a parameter of a sample of a physiological liquid, and
an extending member positioned at the sample inlet port, which member has a surface that is shaped to retain liquid, if wasted, on the member.
In the present context, xe2x80x9csubstantially sealedxe2x80x9d means that access is, in fact, possible to the inner parts of the device in order to be able to introduce the sample therein, but that the device is able to, once the sample has been introduced therein, to hold substantially all sample therein, also during typical handing of the test device or a holder holding the test device.
When introducing liquid into standard test devices of the present type (holding the sample in a cavity), liquid may be spilled from the inlet port due to pressure or volume changes in the test devices or due to any movement thereof. This spilling of sample may be extremely hazardous to laboratory staff. Another problem may arise relating to sample spilled in the apparatus. This sample may constitute a hygiene hazard or problem and may furthermore cause problems if spilled on e.g. sensitive surfaces in the measuring instrumentation. These problems are reduced or avoided using test devices according to the invention.
Preferably, the surface of the extending member comprises one or more grooves so that liquid collected by the member is retained thereon by capillary forces. Naturally, also other types of surfaces, such as surfaces comprising a layer of cloth, felt or the like, may be used.
At present, it is preferred that the test device has an inlet probe positioned at the inlet port in fluid tight communication with the inlet port, the inlet probe having a first end proximate to the inlet port and an opposite second end, and that the extending member extends also to the second end of inlet probe and is adapted to retain liquid on the member if wasted from the second end. The inlet probe may facilitate easy aspiration of sample from a variety of widely used samplers or sample holders, such as syringes.
In order to also allow the use of e.g. capillary tubes, the inlet probe is preferably removably positioned at the inlet port in order to position the capillary directly at the inlet port when aspiring sample therefrom.
As described above, the parameter of the sample of a physiological liquid may be a blood gas parameter, such as pO2, pCO2, pH, haemoglobin, or derivatives of haemoglobin.
It is preferred that the extending member is positioned below the inlet port and/or inlet probe for optimal absorption and retainment of any sample spilled. However, a number of materials or surfaces will, if positioned sufficiently close to the position where the sample is wasted, be able to retain spilled sample, even if positioned at the side or above the inlet port.
A sampling device in which the liquid sample is transported from a patient to the test device or a part of the device may be received by the holder and discarded with the holder. For example, each test device may be adapted to receive and hold the sampling device or a part of thereof so that the (part of the) sampling device may be retained in the holder with the corresponding test device and may be discarded with the holder. The test device preferably comprises fastening means adapted to receive and hold at least a part of a liquid sampling device.
With the present method, system, holder and/or the test devices, spills of liquid sample during the relevant measuring steps is prevented or at least reduced and the number of elements contaminated with contents of the sample to be handled and/or disposed of is reduced and, thus, the risk of laboratory staff being exposed to the sample is greatly reduced.